A Cross-Sectional Study of the Relationship Between Perceived Stress and Thyroid Function Among Apparently Normal Women in the Reproductive Age.

BACKGROUND: A substantial majority of women in India report experiencing stress frequently, with a significant number indicating a lack of time for relaxation. Women within a central productive age bracket often report higher stress levels. Chronic stress can lead to the development of autoimmune disorders affecting the thyroid gland. OBJECTIVE: To evaluate the relationship between perceived stress and thyroid function among apparently normal women of reproductive age. MATERIALS AND METHODS: The present study was conducted at the Vijayanagar Institute of Medical Sciences (VIMS) after obtaining clearance from the Institutional Ethical Committee and informed written consent from the participants. One hundred and fourteen working women aged 20-49 who consented to the study and had no personal or family history of medical illness or thyroid disease were randomly selected. Stress levels were measured using a Perceived Stress Scale (PSS), and thyroid parameters (total triiodothyronine [T3], total thyroxine [T4], and thyroid-stimulating hormone [TSH]) in blood samples were assessed by the electrochemical luminescence immunoassay method. Anthropometric parameters such as age and body mass index (BMI), as well as vital parameters like pulse rate and blood pressure, were measured for all participants. A detailed history was also recorded, including marital status, duration of married life, education, number of children, type of family, per capita income, phase of menstrual cycle, and dietary habits. RESULTS: The Statistical Package for the Social Sciences (SPSS) software version 22.0 was used for statistical analysis. The analysis used Pearson's chi-square test, Student's t-test, and binary logistic regression. A positive correlation was observed between PSS and TSH (correlation coefficient "r" value = 0.060) without a significant p-value. Participants were divided into two groups based on TSH values: those with normal thyroid function (TSH <4.2 international units [IU]) and those with subclinical hypothyroidism (SCH) (TSH >4.2 IU). Both groups had total T3 and T4 levels within the normal reference range. A highly significant difference was observed for age, BMI, TSH, marital status, and duration of married life between women with normal thyroid function and those with SCH. No significant difference was found between the two groups for PSS. DISCUSSION: Both acute and chronic stress affect thyroid function through the hypothalamus-pituitary-thyroid (HPT) axis and the hypothalamus-pituitary-adrenal (HPA) axis. Psychological and physiological stressors induce immune modulations that can lead to autoimmune thyroid diseases, resulting in hypothyroidism. CONCLUSION: The study examined the link between stress and thyroid health in women of childbearing age, revealing a trend where higher stress levels corresponded with increased TSH levels, though not significantly. It also found that older age, higher BMI, and longer duration of marriage were linked to a greater occurrence of SCH. These findings underscore the potential influence of lifestyle factors and stress on thyroid function, suggesting that stress management and demographic factors should be considered in managing thyroid health. For women of reproductive age under high stress, routine monitoring of thyroid function could be beneficial for overall health maintenance.

The interplay between subclinical hypothyroidism and poor sleep quality: A systematic review.

BACKGROUND: The relationship between subclinical hypothyroidism (SHYPO) and sleep disturbances is still poorly investigated. This systematic review aims to critically appraise the existing literature to provide more insights in understanding whether SHYPO favors sleep disturbances or it is the sleep disturbance per se that affects the hypothalamus-pituitary-thyroid axis regulation. METHODS: Original studies on sleep quality and duration in patients with SHYPO were searched in the PubMed/MEDLINE, Embase, Web of Science and Scopus databases. Two reviewers independently screened articles for inclusion, extracted data, and assessed the quality of included studies. RESULTS: Eight studies, including 2916 patients with SHYPO and 18,574 healthy controls, were retrieved. An overall agreement (7 out of 8 studies), about a positive correlation between decreased sleep quality and/or duration and SHYPO was observed. Five studies investigated sleep quality through self-reported surveys; only two studies explored both subjective and objective assessment of sleep quality with actigraphy (n = 1) or polysomnography (n = 1); finally, one study assessed subjective evaluation of sleep quality through a single question regarding the number of sleeping hours. A high level of heterogeneity among studies was manifest due to differences in population source, sleep measure assessment and criteria for diagnosing SHYPO. DISCUSSION: Overall, the existing literature data suggest a link between SHYPO and sleep disturbances, but further studies on larger populations of patients with homogeneous study designs and outcomes are warranted.

Ectopic lingual thyroid with subclinical hypothyroidism in children.

OBJECTIVES: Lingual thyroid is a rare condition that affects approximately 1 in 100,000 individuals. Although it is usually detected in the pediatric population through newborn screening tests or evaluation of congenital hypothyroidism, there are cases in which it remains undetected until adulthood or until symptoms arise because of glandular enlargement. The possible symptoms of lingual thyroid include foreign body sensation in the throat, dysphagia, dyspnea, and hemorrhage. Several cases of lingual thyroid are asymptomatic and accompanied by subclinical hypothyroidism. Herein, we present three cases of lingual thyroid treated with thyroid hormone suppressive therapy. CASE PRESENTATION: The three patients sought medical attention because of a sore throat or foreign body sensation in the throat. Their newborn screening tests and developmental histories were normal. These patients exhibited subclinical hypothyroidism and were treated with hormone suppression therapy. CONCLUSIONS: Patients with lingual thyroid frequently exhibit subclinical hypothyroidism. Hormone treatment may help to reduce the size of the ectopic thyroid and improve symptoms. If an increase in size is noted during follow-up or symptoms do not improve, surgical treatments may be considered.

Effects of levothyroxine in subclinical hypothyroidism and heart failure with reduced ejection fraction: An open-label randomized trial.

We report a randomized, multicenter, open-label trial (ClinicalTrials.gov: NCT03096613) to investigate the clinical benefits of levothyroxine (L-T4) administration in subclinical hypothyroidism (SCH) patients with heart failure with reduced ejection fraction (HFrEF). Overall, 117 patients were enrolled and received L-T4 plus standard HFrEF treatment (experimental group, N = 57) or standard HFrEF therapy alone (control group, N = 60). The change of 6-min walk test distance in the experimental group was significantly higher than that in the control group at 24 weeks (70.08 ± 85.76 m vs. 27.73 ± 82.00 m, mean difference [95% confidence interval (CI)] 46.90 [12.90, 80.90], p < 0.001). Improvements in New York Heart Association (NYHA) classification (p = 0.033) and thyroid function were significant. Adverse event incidence was similar between groups (risk ratio [95% CI]: 0.942 1.053 (0.424, 2.616); p = 0.628). L-T4 addition to HFrEF treatment improved activity tolerance, NYHA class, and thyroid function within 6 months, suggesting its potential for combined therapy in HFrEF patients with SCH. Future double-blind, placebo-controlled trials should be performed to confirm these results.

Vitamin E Intake and Prevalence Rates of Thyroid Dysfunction and Autoimmune Thyroiditis: A Cross-Sectional Analysis of NHANES Data.

Background: Thyroid disorders are associated with various dietary factors and nutritional elements. The aim of this study was to investigate the relationships between dietary vitamin E intake and the prevalence of thyroid dysfunction and thyroid antibody positivity using data from the National Health and Nutrition Examination Survey (NHANES) database. Methods: Data from the NHANES database collected between 2007 and 2012 were analyzed. A total of 7,773 nonpregnant adults without preexisting thyroid diseases and possessing complete thyroid and vitamin E data were included in the study. The participants were categorized into tertiles based on their dietary vitamin E intake: the lowest group (T1: ≤4.53 mg), the intermediate group (T2: 4.54-8.10 mg), and the highest group (T3: ≥8.11 mg). We used a complex multistage probability sampling design in conjunction with R software. We compared thyroid indices, the prevalence of overt and subclinical hyperthyroidism or hypothyroidism, and the occurrence of thyroid antibody positivity among the three groups based on vitamin E intake. Weighted multinomial logistic regression was used to assess the association between dietary vitamin E intake and thyroid disorders. Restricted cubic splines (RCSs) were used to explore potential nonlinear associations. Results: The prevalence rates of subclinical hypothyroidism (SCH) were 3.63%, 3.07%, and 1.85% in T1, T2, and T3, respectively, indicating a decreasing trend (P-trend = 0.013). In the general population, high vitamin E intake (T3) was significantly associated with a lower prevalence of SCH (OR = 0.28, CI = 0.15-0.54, p < 0.001). Subgroup analysis revealed a more pronounced protective effect in males, with both moderate (T2, OR = 0.45, CI = 0.23-0.87, p = 0.020) and high (T3, OR = 0.19, CI = 0.09-0.39, p < 0.001) dietary vitamin E intake being associated with a lower prevalence of SCH. In addition, moderate (T2, OR = 0.59, CI = 0.37-0.93, p = 0.024) and high (T3, OR = 0.52, CI = 0.36-0.75, p < 0.001) dietary vitamin E intake was associated with a lower prevalence of autoimmune thyroiditis (AIT) in males. However, no significant association was observed among females. Conclusion: The findings of this study suggest that a higher intake of vitamin E is associated with lower prevalence rates of SCH and autoimmune thyroiditis among males.

Hypothyroidism and Cardiovascular Disease: A Review.

Hypothyroidism is an endocrine disorder more commonly in older adults. Simultaneously, this population has an increased incidence of cardiovascular risk factors and disease, which remains the leading cause of death worldwide. Thyroid hormones (THs) promote adequate function of the cardiovascular system as they exert their effects through receptors located in the myocardium and the vasculature. In hypothyroidism, this homeostasis is disrupted, which leads to the emergence of pathogenic pathways that accelerate the progression of cardiovascular disease and aggravate its outcomes in these individuals. This article has reviewed existing literature on the relationship between hypothyroidism and cardiovascular disease (CVD). We have explored the pathogenic mechanisms linking both conditions and highlighted the prevalence of cardiovascular risk factors as well as the increased incidence of cardiovascular events in overt and subclinical diseases. Furthermore, indications of hormone replacement therapy in subclinical disease and its efficacy in reducing CVD morbidities in a particular subset of patients have been discussed.

A Comparative Study of Iron Status in Subclinical Hypothyroid and Euthyroid Subjects in a Tertiary Care Hospital.

BACKGROUND: The physiological equilibrium of the entire human body's metabolism is significantly influenced by thyroid hormones. Subclinical hypothyroidism, which is often concealed, is connected to iron deficiency anemia and various other hematological disorders. We in the current study tried to determine the prevalence and severity of iron deficiency anemia and investigate the correlation of subclinical hypothyroidism with iron deficiency. METHODS: A total of 100 subjects included in the study were divided into two groups. Group 1 included 50 cases with subclinical hypothyroidism, and Group 2 included 50 healthy age- and sex-matched controls. Hemoglobin (Hb) levels were measured within 24 hours of sample collection using a Sysmex automated cell counter (Kobe, Hyogo, Japan). Thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH)) were measured. RESULTS: Out of 50 cases, 48 (96%) have iron deficiency anemia, and 52 (104%) have subclinical hypothyroidism. Among the cases with iron deficiency anemia, 43 (86%) also have subclinical hypothyroidism. There was a negative correlation between thyrotropin (TSH) and Hb levels. Pearson's correlation coefficient "r" values were -0.86408. The serum ferritin levels of cases were decreased as compared to the healthy controls, and the difference in means for cases and controls in terms of serum ferritin is also statistically significant. CONCLUSION: The prevalence of anemia in subclinical hypothyroidism is significantly elevated, and considering the absence of significant clinical manifestations in the early stages, it is recommended to routinely conduct investigations for early detection, facilitating prompt management. Consequently, our study emphasizes that both overt and subclinical hypothyroidism should be recognized as risk factors for the development of iron deficiency anemia.

Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

Association of thyroid dysfunction in individuals ≥ 65 years of age with subclinical cardiac abnormalities.

CONTEXT: The relationship between thyroid dysfunction and measures of myocardial disease in older individuals remains to be defined. OBJECTIVE: To evaluate the impact of thyroid dysfunction on structure and function of the left-heart chambers and blood markers of cardiac disease. DESIGN: Cross-sectional analysis. SETTING: The Cardiovascular Health Study, a community-based cohort of older individuals recruited from four urban areas in the United States. PATIENTS: Of 3163 participants studied, 2477 were euthyroid, 465 had subclinical hypothyroidism (SCH), 47 overt hypothyroidism (OH), 45 endogenous (endo) subclinical hyperthyroidism (endo-SCT), and 129 had exogenous (exo) SCT due to thyroid hormone supplementation. INTERVENTIONS: Clinical evaluation, blood sampling and biomarker measurement, 2-dimensional and speckle-tracking echocardiography. MAIN OUTCOME MEASURE(S): Left heart myocardial deformation, circulating biomarkers of diastolic overload (NT-proBNP), fibrosis (sST2, gal-3), and cardiomyocyte injury (hs-cTnT). RESULTS: SCH was associated with higher NT-proBNP (beta = 0.17, p = 0.004), whereas OH was associated with higher hs-cTnT (beta = 0.29, p = 0.005). There were also suggestive associations of SCH with higher sST2, as well as endo-SCT with higher gal-3 and lower (worse) left atrial reservoir strain. Left ventricular longitudinal strain and end-diastolic strain rate did not differ significantly from euthyroid participants in SCH, OH, or exo-SCT. CONCLUSIONS: In this free-living elderly cohort, subclinical and overt hypothyroidism were associated with abnormalities of blood biomarkers consistent with diastolic overload and myocardial necrosis respectively, whereas subclinical hyperthyroidism tended to be associated with myocardial fibrosis and decreased left atrial strain. Our findings could represent stage B heart failure and illuminate distinct aspects of the pathobiology of heart disease related to thyroid gland dysfunction with potential clinical implications.

Prevalence and risk factors for subclinical hypothyroidism in older patients with major depressive disorder.

BACKGROUND: Subclinical hypothyroidism (SCH) is highly correlated with major depressive disorder (MDD). However, the prevalence and risk factors for SCH in older patients with MDD have rarely been reported in China. METHODS: This cross-sectional study included 266 older MDD patients with SCH was performed. Clinical and anthropometric, biochemical, and thyroid function data were collected. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Positive and Negative Syndrome Scale positive subscale, respectively. RESULTS: Among older patients with MDD, the prevalence of SCH was 64.7% (172/266). Compared to patients without SCH, older MDD patients with SCH had a longer disease course and higher TSH, A-TG, A-TPO, HDL-C, LDL-C, TC, FPG, and systolic pressure levels (all P ≤ 0.002). Furthermore, disease progression (OR 1.082, 95% CI 1.020-1.147, P = 0.009), A-TG (OR 1.005, 95% CI 1.001-1.009, P = 0.017), TC (OR 2.024, 95% CI 1.213-3.377, P = 0.007), FPG (OR 2.916, 95% CI 1.637-5.194, P < 0.001), systolic pressure (OR 1.053, 95% CI 1.008-1.100, P = 0.022) were independently associated with SCH, in older patients with MDD. CONCLUSIONS: Our findings suggest a high prevalence of SCH in older patients with MDD. Several demographic and clinical variables were independently associated with SCH in older patients with MDD.

The association between dyslipidaemia in the first trimester and adverse pregnancy outcomes in pregnant women with subclinical hypothyroidism: a cohort study.

BACKGROUND: Subclinical hypothyroidism (SCH) is linked to dyslipidaemia and adverse pregnancy outcomes. However, the impact of dyslipidaemia on the outcome of pregnancy in SCH is unclear. METHODS: We enrolled 36,256 pregnant women and evaluated their pregnancy outcomes. The following data was gathered during the first trimester (≤ 13+ 6 weeks of gestation): total cholesterol (TC), low-density lipoprotein (LDL-C), triglyceride (TG), high-density lipoprotein (HDL-C), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations. The reference ranges for lipids were estimated to range from the 5th to the 95th percentile. Logistic regression assessed the relationships between dyslipidaemia and adverse pregnancy outcomes, including abortion, preeclampsia/eclampsia, low birth weight, foetal growth restriction, premature rupture of foetal membranes, gestational hypertension, preterm birth, macrosomia and gestational diabetes mellitus (GDM). Additionally, the best thresholds for predicting adverse pregnancy outcomes based on TSH, FT4, and lipid levels were determined using receiver operating characteristic curves. RESULTS: In the first trimester, LDL-C > 3.24 mmol/L, TG > 1.92 mmol/L, HDL-C < 1.06 mmol/L, and TC > 5.39 mmol/L were used to define dyslipidaemia. In this cohort, 952 (3.56%) patients were diagnosed with SCH, and those who had dyslipidaemia in the first trimester had higher incidences of gestational hypertension (6.59% vs. 3.25%), preeclampsia/eclampsia (7.14% vs. 3.12%), GDM (22.53% vs. 13.77%), and low birth weight (4.95% vs. 2.08%) than did those without dyslipidaemia. However, after adjusting for prepregnancy body mass index (pre-BMI), dyslipidaemia was no longer related to these risks. Furthermore, elevated TG dyslipidaemia in SCH patients was connected to an enhanced potential of gestational hypertension (odds ratio [OR]: 2.687, 95% confidence interval [CI]: 1.074 ~ 6.722), and elevated LDL-C dyslipidaemia correlated with increased preeclampsia/eclampsia risk (OR: 3.172, 95% CI: 1.204 ~ 8.355) after accounting for age, smoking status, alcohol use, pre-BMI, and levothyroxine use. Additionally, the combination of TC, TG, LDL-C, pre-BMI, and TSH exhibited enhanced predictive capabilities for gestational hypertension, preeclampsia/eclampsia, and GDM. Values of 0.767, 0.704, and 0.706 were obtained from the area under the curve. CONCLUSIONS: Among pregnant women with SCH, dyslipidaemia in early pregnancy was related to elevated risks of adverse pregnancy consequences. The combined consideration of age, pre-BMI, TSH, and lipid levels in the first trimester could be beneficial for monitoring patients and implementing interventions to reduce adverse pregnancy outcomes.

Levothyroxine and Non-alcoholic Fatty Liver Disease: A Mini Review.

Levothyroxine or l-thyroxine is artificially manufactured thyroxine, which is used as a drug to treat underactive thyroid conditions in humans. The drug, levothyroxine, is consumed daily in a prescribed dose to replace the missing thyroid hormone thyroxine in an individual with an underactive thyroid, and it helps to maintain normal physiological conditions. Though it is a life-maintaining drug, it replaces the missing thyroid hormone and performs the necessary daily metabolic functions in our body. Like all other allopathic drugs, it comes with certain side effects, which include joint pain, cramps in muscle, weight gain/loss, hair loss, etc. The thyroid hormone, thyroxine, is known to mobilize fat in our body, including the ones from the hepatic system. An underactive thyroid may cause an accumulation of fat in the liver, leading to a fatty liver, which is clinically termed Non-Alcoholic Fatty Liver Disease (NAFLD). The correlation between hypothyroidism and NAFLD is now well-studied and recognized. As levothyroxine performs the functions of the missing thyroxine, it is anticipated, based on certain preliminary studies, that the drug helps to mobilize hepatic fat and thus may have a crucial role in mitigating the condition of NAFDL.

The Role of Thyroid Hormone Synthesis Gene-Related miRNAs Profiling in Structural and Functional Changes of The Thyroid Gland Induced by Excess Iodine.

At recent years, the impairment caused by iodine excess are paid more attention. However, there is still largely unknown about the exact mechanism induced by excessive iodine. MiRNAs have been found to act as biomarkers for a variety of diseases, whereas fewer studies focused on miRNAs related to a cluster of genes regulating thyroid hormone synthesis, such as NIS, Pendrin, TPO, MCT8, TSHR, TSHα, and TSHß-related miRNAs in structural and functional changes of the thyroid gland induced by subchronic and chronic high iodine exposure. In the present study, one hundred and twenty 4-week-old female Wistar rats were randomly divided into control group (I50µg/L KIO3); HI 1 (I6000µg/L KIO3); HI 2 (I10000µg/L KIO3); and HI 3 (I50000µg/L KIO3), the exposure period was 3 months and 6 months, respectively. The iodine contents in the urine and blood, thyroid function, and pathological changes were determined. In addition, levels of thyroid hormone synthesis genes and the associated miRNAs profiling were detected. The results showed that subclinical hypothyroidism occurred in the high iodine groups with subchronic high iodine exposure, while 6-month exposure led to hypothyroidism in the I10000µg/L and I50000µg/L groups. Subchronic and chronic high iodine exposure caused mRNA and protein levels of NIS, TPO, and TSHR decreased significantly, and Pendrin expression increased significantly. In addition, MCT8 mRNA and protein levels are only remarkably decreased under the subchronic exposure. PCR results showed that levels of miR-200b-3p, miR-185-5p, miR-24-3p, miR-200a-3p, and miR-25-3p increased significantly exposed to high iodine for 3 months, while miR-675-5p, miR-883-5p, and miR-300-3p levels increased significantly under the exposure to high iodine for 6 months. In addition, miR-1839-3p level was markedly decreased exposed to high iodine for 3 and 6 months. Taken together, the miRNA profiling of genes regulating thyroid hormone synthesis remarkably altered from subclinical hypothyroidism to hypothyroidism induced by excess iodine exposure, and some miRNAs may play an important role in subclinical hypothyroidism or hypothyroidism through regulating NIS, Pendrin, TPO, MCT8, and TSHR providing promising targets to alleviate the impairment on the structure and function of thyroid gland.

Impact of levothyroxine therapy for maternal subclinical and overt hypothyroidism on early child neurodevelopment: A prospective cohort study.

OBJECTIVE: Treatment indication of maternal subclinical hypothyroidism (SCH) is undetermined, despite the wide administration of levothyroxine for maternal overt hypothyroidism (OH). This study aimed to evaluate the therapeutic effect of levothyroxine for maternal SCH and OH in real-world practice, with a focus on early child neurodevelopment. DESIGN: Prospective cohort study. PATIENTS AND MEASUREMENTS: Pregnant women diagnosed with SCH at the first antenatal visit were enroled and compared to those diagnosed with OH. Thyroid follow-ups were conducted during pregnancy. Early child neurodevelopment was assessed using the Gesell Development Diagnosis Scale (GDDS) at 1, 3, 6, 12 and 24 months of age. RESULTS: From January 2012 to December 2013, a total of 442 pregnant women were included in final analysis, among whom 194 and 248 were assigned to the SCH and OH groups, respectively. The percentage of levothyroxine therapy at the first antenatal visit was significantly lower in the SCH group than that in the OH group (91.24% vs. 97.58%, p < .01), with a similar treatment rate at delivery (99.4% vs. 100%, p > .05). Notably, GDDS scores were lower in the SCH group than those in the OH group at 6 months to 2 years of age, which was confirmed by subgroup analyses and sensitivity analyses. CONCLUSIONS: Children born with maternal SCH demonstrated slightly lower neuropsychological scores at 6 months to 2 years of age compared to those with maternal OH in the clinical practice. The therapeutic effect of maternal SCH on the child neurodevelopment requires further exploration.

Optimizing levothyroxine treatment for subclinical hypothyroidism during pregnancy.

The onset of pregnancy places additional stress of the thyroid gland, which must produce additional thyroid hormones to support the developing foetus. Hypothyroidism, including subclinical hypothyroidism (SCH), may appear de novo at this time, or existing thyroid disease may become more severe. Accordingly, SCH is a relatively common complication of up to about 3% of pregnancies, with higher rates in some areas. There is strong evidence from systematic reviews and meta-analyses that uncontrolled SCH is associated with an increased risk of adverse pregnancy outcomes, including miscarriage, preeclampsia, and gestational diabetes. The evidence base also suggests that treatment with levothyroxine (LT4), optimized to control thyrotropin (TSH) to within its pregnancy-specific reference ranges reduces these risks. Current management guidelines provide a clear framework of intervention with LT4 in pregnant women with SCH, especially where TSH is high or where thyroperoxidase autoantibodies are present. Sub-optimal adherence to LT4 is common: it is important that patients take their LT4 correctly and that treating physicians and/or healthcare professionals manage these patients according to the latest management guidelines. The titration of LT4 is likely to occur within a range of LT4 daily doses between 25 µg and 75 µg for the majority of this population. LT4 is a narrow therapeutic index drug and small variations in dosage may produce a clinically significant change in thyroid status. Newer formulations of LT4, engineered to provide more precise and consistent dosing, and with a broad range of tablet strengths, may facilitate the precise titration of the LT4 dose for these patients.

Changes in thyroid function and evolution of subclinical thyroid disease in older men.

OBJECTIVE: Prevalence of subclinical thyroid disease increases with age, but optimal detection and surveillance strategies remain unclear particularly for older men. We aimed to assess thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations and their longitudinal changes, to determine the prevalence and incidence of subclinical thyroid dysfunction in older men. DESIGN, PARTICIPANTS AND MEASUREMENTS: Longitudinal study of 994 community-dwelling men aged ≥70 years without known or current thyroid disease, with TSH and FT4 concentrations assessed at baseline and follow-up (after 8.7 ± 0.9 years). Factors associated with incident subclinical thyroid dysfunction were examined by logistic regression and receiver operating characteristic analyses. RESULTS: At baseline, 85 men (8.6%) had subclinical hypothyroidism and 10 (1.0%) subclinical hyperthyroidism. Among 899 men euthyroid at baseline (mean age 75.0 ± 3.0 years), 713 (79.3%) remained euthyroid, 180 (20.0%) developed subclinical/overt hypothyroidism, and 6 (0.7%) subclinical/overt hyperthyroidism. Change in TSH correlated with baseline TSH (r = .16, p < .05). Change in FT4 correlated inversely with baseline FT4 (r = -0.35, p < .05). Only higher age and baseline TSH predicted progression from euthyroid to subclinical/overt hypothyroidism (fully-adjusted odds ratio [OR] per year=1.09, 95% confidence interval [CI] = 1.02-1.17, p = .006; per 2.7-fold increase in TSH OR = 65.4, CI = 31.9-134, p < .001). Baseline TSH concentration ≥2.34 mIU/L had 76% sensitivity and 77% specificity for predicting development of subclinical/overt hypothyroidism. CONCLUSIONS: In older men TSH concentration increased over time, while FT4 concentration showed little change. Subclinical or overt hypothyroidism evolved in one fifth of initially euthyroid men, age and higher baseline TSH predicted this outcome. Increased surveillance for thyroid dysfunction may be justified in older men, especially those with high-normal TSH.

Do elevated thyrotropin levels increase the risk of miscarriages: yes or no?

BACKGROUND: To examine correlation between elevated levels of thyrotropin with the frequency of miscarriages. METHODS: A cross-sectional study was conducted on the 380 respondents and it investigated TSH (thyrotropin), thyroid peroxidase antibody(anti-TPO) and free thyroxine (FT4) in pregnant women who had a miscarriage (N = 179) and pregnant women with normal pregnancies (N = 201). RESULTS: The incidence of subclinical hypothyroidism in the miscarriages group was higher than in control group (61.4% vrs 15.79% (p < 0.001). In the miscarriages group with hypothyroidism (first trimester) mean value of TSH was significantly higher 4.31 ± 2.55 mIU/L compared to the control group 1.95 ± 0.86mIU/L (p < 0.001). Logistic multivariate regression revealed that TSH and body mass index (BMI) have a significant influence on the miscarriage; TSH level has a higher odds ratio (OR) 1.47 CI (95% 1.22-1.78) than BMI (OR) 1.14 CI (95% 1.06-1.23)) (p < 0.001). The combination of thyroid autoimmunity and TSH > 2.5mIU/L increase the risk of miscarriage (65.75%) compared to positive anti-TPO antibodies and TSH < 2.5mIU/L(14.15%)(p < 0.001). CONCLUSIONS: Higher TSH levels correspond with obesity during early pregnancy and may be a sign of maternal thyroid dysfunction. Physiological thyroid function in the first trimester of pregnancy is important for perinatal outcome.

Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults.

CONTEXT: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. OBJECTIVE: To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism. DESIGN: Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial). SETTING: Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. PARTICIPANTS: The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. MAIN OUTCOME MEASURES: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. RESULTS: In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. CONCLUSION: Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01660126 and Netherlands Trial Register, NTR3851.

Association Between Maternal Thyroid Function in Early Pregnancy and Gestational Diabetes: A Prospective Cohort Study.

CONTEXT: Previous studies on the relationship between thyroid gland function and the development of gestational diabetes mellitus (GDM) have reported different results, leading to the need for a cohort study design with a large sample size. OBJECTIVE: We aimed to investigate the relationship between thyroid function in early pregnancy and GDM. METHODS: This was a prospective cohort study based on the China Birth Cohort Study (CBCS), from February 2018 to December 2020. The study took place at a tertiary maternal and child health hospital. A total of 36 256 pregnant women were successfully recruited based on the CBCS. The main outcome measure was GDM. RESULTS: This study consisted of 26 742 pregnant women who met the inclusion criteria, of whom 3985 (14.90%) were diagnosed with GDM, and the women with GDM were older than their healthy counterparts (33.26 ± 4.01 vs 31.51 ± 3.76 years, P < .001). After removing potential influencing variables, we found that increased thyroid-stimulating hormone (TSH) (adjusted odds ratio [aOR] 1.030, 95% CI 1.007, 1.054, P = .012) and subclinical hypothyroidism (aOR 1.211, 95% CI 1.010, 1.451, P = .039), but not free thyroxine or thyroid peroxidase antibody, were associated with the occurrence of GDM. Further analysis indicated a nonlinear relationship between TSH and GDM (P < .05): when TSH ≤ 1.24 mIU/L, the occurrence of GDM was elevated with increasing TSH, but when TSH > 1.24 mIU/L, this trend was not obvious. CONCLUSION: High TSH might be associated with increased risk of GDM.

The risk of developing gestational diabetes mellitus in maternal subclinical hypothyroidism: a systematic review and meta-analysis.

PURPOSE: The purpose of this study was to determine the association between maternal subclinical hypothyroidism (SCH) and gestational diabetes mellitus (GDM) risk. METHODS: This study is a systematic review and meta-analysis. Following PubMed, Medline, Scopus, Web of Science, and Google Scholar database search up to April 1 2021, a total of 4597 studies were identified. Studies published in English, with full text available, related to subclinical hypothyroidism in pregnancy, reporting or mentioning the incidence of GDM were included in the analysis. Following exclusion of studies, a total of 16 clinical trial were analyzed. For the risk of GDM, odds ratios (ORs) were calculated. Subgroup analyzes were performed according to gestational age and thyroid antibodies. RESULTS: Pregnant women with SCH were at increased risk of GDM compared to women with euthyroidism, overall (OR = 1.339, 95% CI 1.041-1.724; p = 0.023). Additionally, SCH without thyroid antibodies has no significant effect on GDM risk (OR = 1.173, 95% CI 0.88-1.56; p = 0.277) and pregnant women with SCH in the first trimester were not found to be at increased risk of GDM compared to women with euthyroidism regardless of thyroid antibodies (OR = 1.088, 95%CI 0.816-1.451; p = 0.564). CONCLUSIONS: Maternal SCH in pregnancy is related to an increased risk of GDM.